This is a project to study the regulation of carbon pathways in intermediary metabolism of liver and heart which might delineate the biochemical abnormalities fundamental to the understanding of the pathophysiology of diabetes mellitus and myocardial ischemia. Isolated cells, mitochondria, submitochondrial particles and reconstituted systems incorporated into liposomes from liver and heart tissue will be used to study the mechanism fatty acyl CoA esters. The binding of fatty acyl CoA esters to the cytosolic fatty acid binding protein as determined by the competitive binder, flavaspidic acid, will be studied to relate their potential effectiveness as ligands for the adenine nucleotide translocase. The reversible inhibition of certain mitochondrial metabolite transport systems by long chain fatty acyl CoA esters will be correlated with the resulting effects on gluconeogenesis, lipogenesis and fatty acid oxidation. The protozoan, Tetrahymena Pyriformis will be used as an experimental model system for diabetes in which the modulation of gluconeogenesis can be studied as a function of protein synthesis. Two new proteins, an inhibitor of aminoacylation of tRNA and a cytosolic Ca ions ATPase recently isolated from Tetrahymena will be further characterized and related to the metabolism and function of the organism.